Drug Therapy in Lupus Nephropathy

April 8, 2008 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Immunosuppressive Drug Therapy in Membranous Lupus Nephropathy

Studies have shown that up to 26% of patients with systemic lupus erythematoses nephritis may suffer from membranous lupus nephropathy. The disease is characterized by high levels of protein in the urine and may eventually lead to kidney failure.

This study will evaluate the effectiveness and toxic effects of immunosuppressive drug therapy in patients with membranous lupus nephropathy over a 12 month period. The major goal of this therapy is to decrease protein losses and ultimately prevent kidney failure.

Patients enrolled in the study will undergo a routine history and physical examination. In addition, several diagnostic tests will be conducted including; chest x-ray ECG, blood and urine laboratory tests.

Patients will be divided and grouped according to the severity of their disease as shown by kidney function. Each group will then randomly be subcategorized by different treatment plans. Each treatment plan will made up of immunosuppressive medications including prednisone, cyclophosphamide, cyclosporin A, and combinations of these drugs. Patients will receive the medications as directed by the study.

The study will last 12 months and require patients to be admitted for two to five days before the study begins and once the study is completed. Patients will be followed as outpatients throughout the 12 month study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase 2 trial to evaluate the effectiveness and toxicity of immunosuppressive drug therapy in patients with membranous lupus nephropathy over a 12 month study period. Patients with renal biopsy documented membranous nephropathy will all be treated with alternate day prednisone and will be randomized to receive: a) no additional therapy (control group), b) intravenous cyclophosphamide up to 1.0 gm per m(2) body surface area every other month for 6 total doses, or c) oral cyclosporin A up to 200 mg per m(2) body surface area daily for a total of 11 months. Patients with glomerular filtration rates 25-66 ml/min will be randomized only to prednisone alone or to prednisone plus cyclophosphamide. Renal function and disease activity will be monitored throughout the study; physiologic measures of glomerular function (GFR, permselectivity) will be examined at study entry and at the conclusion of the study. Comparison will be made of the number of favorable outcomes of glomerular function as well as drug related toxicities achieved by each treatment group at the end of the 12th study month.

Study Type

Interventional

Enrollment

45

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA - All patients admitted to the study must satisfy each of the following criteria:

Ability to provide informed consent to all aspects of the study after full information is provided.

SLE as defined by the presence of at least 4 criteria established by the American Rheumatism Association.

Age 12 years or older.

Membranous lupus nephropathy manifested by 2 or more grams per day of proteinuria in the absence of infection or recognized non-lupus renal disease. A renal biopsy must reveal typical membranous lupus nephropathy by light microscopy. Immune deposits must be predominately sub-epithelial and/or intramembranous in location by electron microscopy.

EXCLUSION CRITERIA - Patients with any one of the following conditions will be excluded:

Medication history of:

  • cytotoxic drugs or cyclosporin A for more than 2 weeks during the 10 week period prior to study entry.
  • cytotoxic drug therapy or cyclosporin A for more than 10 weeks at anytime in the past.
  • cytotoxic drug therapy or cyclosporin A during the 30 day period prior to study entry.
  • requirement of corticosteroids in doses greater than 20 mg/m(2)/day of prednisone (or equivalent) for control of extrarenal disease at the time of study entry.

Active acute or chronic infection requiring antimicrobial therapy, or serious viral infection (eg. hepatitis, herpes zoster).

Pregnant females, nursing mothers, or females not practicing birth control.

Patients with a single functioning kidney.

Pre-existent malignancy.

Insulin-treated diabetes mellitus.

GFR less than 25 ml/min/1.73m(2) BSA.

Known toxicity to cyclophosphamide.

Positive tests for HIV infection.

Furthermore, patients with any one of the following conditions (related to the use of cyclosporin A) will be excluded from randomization within renal function group 2 (Glomerular filtration rate greater than 66 ml/min/1.73m(2)):

  • Renal biopsy revealing global sclerosis of greater than 50 percent of glomeruli, severe tubular atrophy, or severe interstitial fibrosis.
  • Persistently abnormal and unexplained liver function abnormalities (defined as elevated transaminases, bilirubin, or alkaline phosphatase twice the upper limit of normal for at least 1 month) or evidence of active viral hepatitis.
  • Hypertension difficult to control or uncontrollable with conventional anti-hypertensive regimens.
  • Documented coronary artery disease.
  • Convulsive disorders.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to complete or partial remission of proteinuria.
Time Frame: Within the firs year after starting protocol treatment
Within the firs year after starting protocol treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in glomerular filtration rate
Time Frame: One year
One year
Adverse Effects
Time Frame: For the duration of extended follow-up starting at the beginning of protocol treatment
For the duration of extended follow-up starting at the beginning of protocol treatment
Time to relapse of nephritic syndrome
Time Frame: For the duration of extended follow-up starting at the end of the 12-month protocol treatment period
For the duration of extended follow-up starting at the end of the 12-month protocol treatment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1986

Study Completion

September 1, 2004

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

November 3, 1999

First Posted (Estimate)

November 4, 1999

Study Record Updates

Last Update Posted (Estimate)

April 9, 2008

Last Update Submitted That Met QC Criteria

April 8, 2008

Last Verified

April 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 860204
  • 86-DK-0204

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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